tbuckley/cabot-search huggingface dataset:
The evolution of digital health technologies in cardiovascular disease research
Authors: Clara C. Zwack, Milad Haghani, Matthew Hollings, Ling Zhang, Sarah Gauci, Robyn Gallagher, Julie Redfern
Journal: npj Digital Medicine (2023)

Abstract When implemented in practice, digital technologies have shown improvements in morbidity and mortality outcomes in patients with cardiovascular disease (CVD). For scholars, research into digital technologies in cardiovascular care has been relatively recent, thus it is important to understand the history of digital health technology in cardiovascular research—its emergence, rate of growth, hot topics, and its temporal evolution. The aim of this study was to analyse more than 16,000 articles in this domain based on their scientometric indicators. Web of Science (WoS) Core Collection was accessed and searched at several levels, including titles, abstracts, keywords, authors, sources and individual articles. Analysis examined the temporal shifts in research and scholarly focus based on keywords, networks of collaboration, topical divisions in relation to digital technologies, and influential publications. Findings showed this research area is growing exponentially. Co-citation analysis revealed twenty prominent research streams and identified variation in the magnitude of activities in each stream. A recent emergence of research activities in digital technology in cardiovascular rehabilitation (CR), out-of-hospital cardiac arrest (OHCA), and arrythmia research was also demonstrated. Conversely, wearable technologies, activity tracking and electronic medical records research are now past their peak of reported research activity. With increasing amounts of novel technologies becoming available and more patients taking part in remote health care monitoring, further evaluation and research into digital technologies, including their long-term effectiveness, is needed. Furthermore, emerging technologies, which are evaluated and/or validated should be considered for implementation into clinical practice as treatment and prevention modalities for CVD.
TRIM27 maintains gut homeostasis by promoting intestinal stem cell self-renewal
Authors: Jing Wang, Dongdong Zhao, Zehui Lei, Pupu Ge, Zhe Lu, Qiyao Chai, Yong Zhang, Lihua Qiang, Yang Yu, Xinwen Zhang, Bingxi Li, Shu Zhu, Lingqiang Zhang, Cui Hua Liu
Journal: Cellular and Molecular Immunology (2023)
Circulating Spike Protein Detected in Post–COVID-19 mRNA Vaccine Myocarditis
Authors: Lael M. Yonker, Zoe Swank, Yannic C. Bartsch, Madeleine D. Burns, Abigail Kane, Brittany P. Boribong, Jameson P. Davis, Maggie Loiselle, Tanya Novak, Yasmeen Senussi, Chi-An Cheng, Eleanor Burgess, Andrea G. Edlow, Janet Chou, Audrey Dionne, Duraisamy Balaguru, Manuella Lahoud-Rahme, Moshe Arditi, Boris Julg, Adrienne G. Randolph, Galit Alter, Alessio Fasano, David R. Walt
Journal: Circulation (2023)

Cases of adolescents and young adults developing myocarditis after vaccination with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-targeted mRNA vaccines have been reported globally, but the underlying immunoprofiles of these individuals have not been described in detail.
Efficacy of omecamtiv mecarbil in heart failure with reduced ejection fraction according to N‐terminal pro‐B‐type natriuretic peptide level: insights from the GALACTIC‐HF trial
Authors: Kieran F. Docherty, John J.V. McMurray, Brian L. Claggett, Zi Michael Miao, Kirkwood F. Adams, Alexandra Arias‐Mendoza, John G.F. Cleland, Rafael Diaz, Luis E Echeverria Correa, G. Michael Felker, Candida Fonseca, Jing Li, Marco Metra, Karen Sliwa‐Hahnle, Scott D. Solomon, Hans J. Vandekerckhove, Dragos Vinereanu, Adriaan A. Voors, Stephen B. Heitner, Stuart Kupfer, Fady I. Malik, Lisa Meng, John R. Teerlink
Journal: European Journal of Heart Failure (2023)

N-terminal pro-B-type natriuretic peptide (NT-proBNP) is predictive of both outcomes and response to treatment in patients with heart failure with reduced ejection fraction (HFrEF). The aim of this study was to examine the effect of the cardiac myosin activator omecamtiv mecarbil according to baseline NT-proBNP level in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure trial (GALACTIC-HF).The primary outcome was the composite of a worsening heart failure event (urgent clinic visit, emergency department visit, or hospitalization) or cardiovascular death. We prespecified analysis of the effect of treatment according to baseline NT-proBNP (≤ median, > median), excluding individuals with atrial fibrillation/flutter (AF/AFL). Of the 8232 patients analysed, 8206 had an available baseline NT-proBNP measurement. Among the 5971 patients not in AF/AFL, the median (Q1-Q3) NT-proBNP level was 1675 (812-3579) pg/ml. Hazard ratios (HR) for the effect of omecamtiv mecarbil, compared with placebo, for the primary endpoint in patients without AF/AFL were: ≤ median 0.94 (95% confidence interval [CI] 0.80-1.09), > median 0.81 (0.73-0.90) (p-interaction = 0.095); for the overall population (including patients with AF/AFL) the HRs were ≤ median 1.01 (0.90-1.15) and > median 0.88 (0.80-0.96) (p-interaction = 0.035). There was an interaction between treatment and NT-proBNP, examined as a continuous variable, with greater effect of omecamtiv mecarbil on the primary outcome in patients with a higher baseline NT-proBNP (p-interaction = 0.086).In GALACTIC-HF, the benefit of omecamtiv mecarbil appeared to be larger in patients with higher baseline NT-proBNP levels, especially in patients without AF/AFL.ClinicalTrials.gov Identifier NCT02929329; EudraCT number, 2016-002299-28.
Diaphragm Muscle Weakness Might Explain Exertional Dyspnea 15 Months after Hospitalization for COVID-19
Authors: Binaya Regmi, Janina Friedrich, Benedikt Jörn, Mehdi Senol, Alberto Giannoni, Matthias Boentert, Ayham Daher, Michael Dreher, Jens Spiesshoefer
Journal: American Journal of Respiratory and Critical Care Medicine (2023)

Rationale: Dyspnea is often a persistent symptom after acute coronavirus disease (COVID-19), even if cardiac and pulmonary function are normal. Objectives: This study investigated diaphragm muscle strength in patients after COVID-19 and its relationship to unexplained dyspnea on exertion. Methods: Fifty patients previously hospitalized with COVID-19 (14 female, age 58 ± 12 yr, half of whom were treated with mechanical ventilation, and half of whom were treated outside the ICU) were evaluated using pulmonary function testing, 6-minute-walk test, echocardiography, twitch transdiaphragmatic pressure after cervical magnetic stimulation of the phrenic nerve roots, and diaphragm ultrasound. Diaphragm function data were compared with values from a healthy control group. Measurements and Main Results: Moderate or severe dyspnea on exertion was present at 15 months after hospital discharge in approximately two-thirds of patients. No significant pulmonary function or echocardiography abnormalities were detected. Twitch transdiaphragmatic pressure was significantly impaired in patients previously hospitalized with COVID-19 compared with control subjects, independent of initial disease severity (14 ± 8 vs. 21 ± 3 cm H2O in mechanically ventilated patients vs. control subjects [P = 0.02], and 15 ± 8 vs. 21 ± 3 cm H2O in nonventilated patients vs. control subjects [P = 0.04]). There was a significant association between twitch transdiaphragmatic pressure and the severity of dyspnea on exertion (P = 0.03). Conclusions: Diaphragm muscle weakness was present 15 months after hospitalization for COVID-19 even in patients who did not require mechanical ventilation, and this weakness was associated with dyspnea on exertion. The current study, therefore, identifies diaphragm muscle weakness as a correlate for persistent dyspnea in patients after COVID-19 in whom lung and cardiac function are normal. Clinical trial registered with www.clinicaltrials.gov (NCT04854863).
Transcatheter edge‐to‐edge repair for secondary mitral regurgitation with third‐generation devices in heart failure patients – results from the Global <scp>EXPAND</scp> Post‐Market study
Authors: Mathias Orban, Wolfgang Rottbauer, Mathew Williams, Paul Mahoney, Ralph Stephan von Bardeleben, Matthew J. Price, Carmelo Grasso, Philipp Lurz, Jose L. Zamorano, Federico M. Asch, Francesco Maisano, Saibal Kar, Jörg Hausleiter
Journal: European Journal of Heart Failure (2023)

Mitral valve transcatheter edge-to-edge repair is a guideline-recommended treatment option for patients with secondary mitral regurgitation (SMR). The purpose of this analysis was to report contemporary real-world outcomes in SMR patients treated with third-generation MitraClip systems.EXPAND is a prospective, multicentre, international, single-arm study with 1041 patients treated for mitral regurgitation (MR) with MitraClip NTR/XTR, with 30-day and 1-year follow-up. All echocardiograms were analysed by an independent echocardiographic core lab. Study outcomes included procedural outcomes, durability of MR reduction, and major adverse events including all-cause mortality and heart failure hospitalizations (HFH). A subgroup of 413 symptomatic patients (age 74.7 ± 10.1 years, 58% male) with severe SMR were included. MR reduction to MR ≤ 1+ and MR ≤ 2+ was achieved in 93.0% and 98.5% of patients, respectively, which was sustained at 1-year follow-up. All-cause mortality was 17.7% at 1-year- follow-up, and the combined endpoint of all-cause mortality or first HFH occurred in 34% of patients. This combined endpoint was significantly less frequently observed in MR ≤ 1+ patients (Kaplan-Maier estimates: 29.7% vs. 69.6% for MR ≤ 1+ vs. MR ≥ 2 +; p < 0.0001). New York Heart Association (NYHA) functional class improved significantly from baseline (NYHA ≤ II: 17%) to 1-year follow-up (NYHA ≤ II: 78%) (p < 0.0001). While MR reduction was comparable between NTR-only vs. XTR-only treated patients, less XTR clips were required for achieving MR reduction.Under real-world conditions, optimal sustained MR reduction to MR ≤ 1+ was achieved in a high percentage of patients with third-generation MitraClip, which translated into symptomatic improvement and low event rates. These results appear to be comparable with recent randomized clinical trials.
Exercise Volume Versus Intensity and the Progression of Coronary Atherosclerosis in Middle-Aged and Older Athletes: Findings From the MARC-2 Study
Authors: Vincent L. Aengevaeren, Arend Mosterd, Esmée A. Bakker, Thijs L. Braber, Hendrik M. Nathoe, Sanjay Sharma, Paul D. Thompson, Birgitta K. Velthuis, Thijs M.H. Eijsvogels
Journal: Circulation (2023)

Physical activity and exercise training are associated with a lower risk for coronary events. However, cross-sectional studies in middle-aged and older male athletes revealed increased coronary artery calcification (CAC) and atherosclerotic plaques, which were related to the amount and intensity of lifelong exercise. We examined the longitudinal relationship between exercise training characteristics and coronary atherosclerosis. Middle-aged and older men from the MARC-1 (Measuring Athlete's Risk of Cardiovascular Events 1) study were invited for follow-up in MARC-2 (Measuring Athlete's Risk of Cardiovascular Events 2) study. The prevalence and severity of CAC and plaques were determined by coronary computed tomography angiography. The volume (metabolic equivalent of task [MET] hours/week) and intensity (moderate [3 to 6 MET hours/week]; vigorous [6 to 9 MET hours/week]; and very vigorous [≥9 MET hours/week]) of exercise training were quantified during follow-up. Linear and logistic regression analyses were performed to determine the association between exercise volume/intensity and markers of coronary atherosclerosis. We included 289 (age, 54 [50 to 60] years [median (Q1 to Q3)]) of the original 318 MARC-1 participants with a follow-up of 6.3±0.5 years (mean±SD). Participants exercised for 41 (25 to 57) MET hours/week during follow-up, of which 0% (0 to 19%) was at moderate intensity, 44% (0 to 84%) was at vigorous intensity, and 34% (0 to 80%) was at very vigorous intensity. Prevalence of CAC and the median CAC score increased from 52% to 71% and 1 (0 to 32) to 31 (0 to 132), respectively. Exercise volume during follow-up was not associated with changes in CAC or plaque. Vigorous intensity exercise (per 10% increase) was associated with a lesser increase in CAC score (β, -0.05 [-0.09 to -0.01]; P=0.02), whereas very vigorous intensity exercise was associated with a greater increase in CAC score (β, 0.05 [0.01 to 0.09] per 10%; P=0.01). Very vigorous exercise was also associated with increased odds of dichotomized plaque progression (adjusted odds ratio [aOR], 1.09 [1.01 to 1.18] per 10%; aOR, 2.04 [0.93 to 4.15] for highest versus lowest very vigorous intensity tertiles, respectively), and specifically with increased calcified plaques (aOR, 1.07 [1.00 to 1.15] per 10%; aOR, 2.09 [1.09 to 4.00] for highest versus lowest tertile, respectively). Exercise intensity but not volume was associated with progression of coronary atherosclerosis during 6-year follow-up. It is intriguing that very vigorous intensity exercise was associated with greater CAC and calcified plaque progression, whereas vigorous intensity exercise was associated with less CAC progression.
YAP-Activated SATB2 Is a Coactivator of NRF2 That Amplifies Antioxidative Capacity and Promotes Tumor Progression in Renal Cell Carcinoma
Authors: Juan Jin, Fen Chen, Wenfang He, Li Zhao, Bo Lin, Danna Zheng, Li Chen, Hongchao He, Qiang He
Journal: Cancer Research (2023)

Abstract Aberrant epigenetic reprogramming contributes to the progression of renal cell carcinoma (RCC). Elucidation of key regulators of epigenetic reprogramming in RCC could help identify therapeutic vulnerabilities to improve treatment. Here, we report upregulation of the nuclear matrix-associated protein, special AT-rich binding protein-2 (SATB2), in RCC samples, which correlated with poor prognosis. SATB2 inhibition suppressed RCC growth and self-renewal capacities. YAP/TEAD4 activated SATB2 expression and depended on SATB2 to enhance cell proliferation. Transcriptome analysis implicated that SATB2 regulates NRF2 downstream targets to suppress oxidative stress without altering NRF2 levels. Integrated chromatin immunoprecipitation sequencing and assay for transposase-accessible chromatin using sequencing analyses demonstrated that SATB2 coordinated with NRF2 to drive enhancer–promoter interactions, amplifying transcriptional activity. SATB2 recruited SWI/SNF complex subunits, including BRD7 or BRG1, to sustain DNA accessibility. Increased SATB2 triggered chromatin remodeling into configurations that rendered RCC more sensitive to SATB2 deficiency. Moreover, SATB2 ablation promoted the sensitivity of RCC to chemotherapy-induced apoptosis. Finally, targeting SATB2 or BRD7 effectively restricted the proliferation of YAP-high tumors in patient-derived xenografts and patient-derived organoids. Together, SATB2 is an oncogenic chromatin organizer in RCC, and targeting SATB2 is an effective strategy to suppress the YAP-high RCC. Significance: A YAP-SATB2-NRF2 regulatory axis amplifies antioxidative stress signaling and provides potential therapeutic targets to enhance response to chemotherapy in renal cell carcinoma.
Autologous Th2‐polarized lymphocytes induce atopic dermatitis lesions in non‐atopic human skin xenotransplants
Authors: Aviad Keren, Kristian Reich, Marta Bertolini, Alain Moga, Christoph Riethmüller, Yehuda Ullmann, Ralf Paus, Amos Gilhar
Journal: Allergy (2023)

The key signals that suffice to induce atopic dermatitis (AD) in human skin remain incompletely understood. Also, current mouse models reflect human AD only unsatisfactorily. Therefore, we have asked whether a humanized AD mouse model can be developed that reflects human AD more faithfully and permit to identify key signals that suffice to induce AD lesions in previously healthy human skin in vivo.Healthy human skin from non-atopic donors was transplanted onto SCID/beige mice. After xenotransplant reinnervation by mouse sensory nerve fibers had occurred, mixed autologous human Th2 CD4+ and Tc2 CD8+ T cells that had been pretreated in vitro with IL-2, IL-4, and LPS were injected intradermally into the xenotransplants without skin barrier disruption.Injected non-atopic xenotransplants rapidly developed a morphological, functional, and immunological phenocopy of human AD lesions regarding skin barrier defects, immunopathology including intraepidermal eosinophils, mast cell activation, increase of thymic stromal lymphopoietin, eotaxin-1 and type 2 cytokine circuits, and even showed characteristic neuroimmunological abnormalities such as ß2-adrenergic receptor downregulation. The experimentally induced AD lesions in human skin responded to standard AD therapy (topical dexamethasone or tacrolimus; systemic anti-IL-4Rα antibody [dupilumab]), and relapsed when neurogenic skin inflammation was induced by exposing mice to perceived stress.This new animal model uniquely mimics the complexity of human AD and its clinical response to standard therapy and psychoemotional stressors in vivo, and shows that Th2-polarized lymphocytes associated with excessive IL-4Rα-mediated signaling suffice to induce human AD skin lesions, while atopy and epidermal barrier disruption are dispensable.
Highlights from Recent Cancer Literature
Journal: Cancer Research (2023)

Alternative Splicing Modulates GlioblastomaGlioblastoma tumors are spatially heterogenous and support the existence of many unique tumor cell populations, complicating the issue of how to effectively target these tumors therapeutically.Larionova and colleagues studied differential transcripts between the glioblastoma core and periphery using RNA sequencing and mass spectrometry.Ribosomes in the core and periphery of the tumor differed due to alternative RNA splicing.Specifically, the authors identified a switch from the Ribosomal Protein L22 Like 1 (RPL22L1) to the RPL22L1b isoform, which conferred increased stemness potential to glioblastoma cells.Mice bearing glioma xenografts expressing RPL22L1b had decreased survival compared with xenografts expressing RPL22L1a.The RPL22L1b isoform interacted with the lncRNA MALAT1, a putative tumor suppressor, to promote its degradation.Moreover, the authors identified that serine and argininerich splicing factor 4 (SRSF4) regulated RPL22L1 mRNA splicing.While no SRSF4-specific inhibitor exists, the authors were able to show that FG1059, a dual CLK1/4 inhibitor and positive regulator of SRSF4, reduced the RPL22L1b isoform and extended survival of patient-derived xenograft models of glioblastoma.
HAND2 Assists MYCN Enhancer Invasion to Regulate a Noradrenergic Neuroblastoma Phenotype
Authors: Man Xu, Ming Sun, Xiyuan Zhang, Rosa Nguyen, Haiyan Lei, Jack F. Shern, Carol J. Thiele, Zhihui Liu
Journal: Cancer Research (2023)

Noradrenergic neuroblastoma is characterized by a core transcriptional regulatory circuitry (CRC) comprised of transcription factors (TF) such as PHOX2B, HAND2, and GATA3, which form a network with MYCN. At normal physiologic levels, MYCN mainly binds to promoters but when aberrantly upregulated as in neuroblastoma, MYCN also binds to enhancers. Here, we investigated how MYCN invades enhancers and whether CRC TFs play a role in this process. HAND2 was found to regulate chromatin accessibility and to assist MYCN binding to enhancers. Moreover, HAND2 cooperated with MYCN to compete with nucleosomes to regulate global gene transcription. The cooperative interaction between MYCN and HAND2 could be targeted with an Aurora A kinase inhibitor plus a histone deacetylase inhibitor, resulting in potent downregulation of both MYCN and the CRC TFs and suppression of MYCN-amplified neuroblastoma tumor growth. This study identifies cooperation between MYCN and HAND2 in neuroblastoma and demonstrates that simultaneously targeting MYCN and CRC TFs is an effective way to treat this aggressive pediatric tumor.HAND2 and MYCN compete with nucleosomes to regulate global gene transcription and to drive a malignant neuroblastoma phenotype.
Parkinson’s Disease Genes VPS35 and EIF4G1 Interact Genetically and Converge on α-Synuclein
Authors: Nripesh Dhungel, Simona Eleuteri, Ling-bo Li, Nicholas J. Kramer, Justin W. Chartron, Brian Spencer, Kori Kosberg, Jerel Adam Fields, Klodjan Stafa, Anthony Adame, Hilal Lashuel, Judith Frydman, Kang Shen, Eliezer Masliah, Aaron D. Gitler
Journal: Neuron (2023)
Microglia drive transient insult-induced brain injury by chemotactic recruitment of CD8+ T lymphocytes
Authors: Zhongshan Shi, Pei Yu, Wei-Jye Lin, Sitai Chen, Xia Hu, Siqi Chen, Jinping Cheng, Qiang Liu, Yuhua Yang, Shaojian Li, Zhan Zhang, Jiatian Xie, Jingru Jiang, Baixuan He, Yi Li, Honghong Li, Yongteng Xu, Junbo Zeng, Jialin Huang, Jinghong Mei, Jinhua Cai, Jiongxue Chen, Long-Jun Wu, Ho Ko, Yamei Tang
Journal: Neuron (2023)
Design and Development of Extracellular Matrix Protein‐Based Microcapsules as Tools for Bacteria Investigation
Authors: Sadaf Pashapour, Senne Seneca, Martin Schröter, Friedrich Frischknecht, Ilia Platzman, Joachim Spatz
Journal: Advanced Healthcare Materials (2023)

The extracellular matrix (ECM) plays an immense role in the homeostasis of tissues and organs, can function as a barrier for infectious agents, but is also exploited by pathogens during infection. Therefore, the development of well-defined 3D ECM models in the form of microcapsules to elucidate the interactions between ECM components and pathogens in confinement and study disease infectivity is important, albeit challenging. Current limitations are mainly attributed to the lack of biocompatible methods for the production of protein-based microcapsules. Herein, hollow ECM-based microcapsules from laminin-111 or laminin-111/collagen IV are generated to investigate the behavior of organisms within confined 3D extracellular matrices. Microcapsules are created using water-in-oil emulsion droplets stabilized by block copolymer surfactants as templates for the charge-mediated attraction of laminin or laminin-collagen proteins to the droplets' inner periphery, allowing for the formation of modular ECM-based microcapsules with tunable biophysical and biochemical properties and organism encapsulation. The release of E. coli-laden ECM-based protein microcapsules into a physiological environment revealed differences in the dynamic behavior of E. coli depending on the constitution of the surrounding ECM protein matrix. The developed ECM-based protein microcapsules have the potential to be implemented in several biomedical applications, including the design of in vitro infection models.